Total Synthesis of Malacidin A by β-Hydroxyaspartic Acid Ligation-Mediated Cyclization and Absolute Structure Establishment

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

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Author(s)

  • Zhenquan Sun
  • Zhuo Shang
  • Nicholas Forelli
  • Kathy Hiu Laam Po
  • Sean F Brady
  • Xuechen Li

Detail(s)

Original languageEnglish
Journal / PublicationAngewandte Chemie - International Edition
Publication statusOnline published - 29 Jul 2020

Abstract

The development of novel antibiotics is critical to combating the growing emergence of drug-resistant pathogens. Malacidin A is a new member of the calcium-dependent antibiotic (CDAs) family with activity against antibiotic-resistant pathogens. Its mode of action is distinct from classical CDAs. However, the absolute structure of malacidin A has not been established. Herein, the total syntheses of malacidin A and its analogues are reported by a combination of Fmoc-based solid-phase peptide synthesis (SPPS) and β-hydroxyaspartic acid ligation-mediated peptide cyclization. The total synthesis enabled us to establish the absolute configuration of malacidin A, which is in agreement with those for natural malacidin A confirmed by advanced Marfey's analysis in our study.

Research Area(s)

  • chemical ligation, cyclic peptide antibiotics, malacidin, total synthesis, β-hydroxyaspartic acid

Citation Format(s)

Total Synthesis of Malacidin A by β-Hydroxyaspartic Acid Ligation-Mediated Cyclization and Absolute Structure Establishment. / Sun, Zhenquan; Shang, Zhuo; Forelli, Nicholas; Po, Kathy Hiu Laam; Chen, Sheng; Brady, Sean F; Li, Xuechen.

In: Angewandte Chemie - International Edition, 29.07.2020.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal